This NIH K23 proposal described a 4 year training and research plan for the candidate, a physician scientist with a long term goal of becoming an independent investigator with expertise in neonatal clinical trials with a focus on neonatal resuscitation, optimization of oxygen (O2) therapy in the newborn and prevention of oxidative stress related morbidities. To accomplish these goals, the candidate and his mentors put forth an integrated plan encompassing a novel research idea and training in oxidative stress pathophysiology and clinical trials with a focus on neonatal resuscitation. Premature infants have high incidence of various morbidities leading to poor neurodevelopment and mortality. Oxidative stress plays an important role in the pathophysiology of many of these morbidities. The use of high O2 concentrations, even for brief periods during delivery room (DR) resuscitation exacerbates the generation of reactive O2 species which can overwhelm newborn antioxidant capacity and may damage various organs. In preterm infants, multiple small clinical studies have shown that a reduction in the O2 load in the DR decreases oxidative stress and improves clinical outcomes. However, definitive evidence from appropriately powered randomized controlled trial is lacking. Studies have demonstrated that in healthy term newborns it takes at least 5 minutes after birth for the oxygen saturation (SpO2) to rise from around 50% to greater than 90%. These are called the transitional goal SpO2. In previous studies, the candidate has demonstrated the feasibility of initiating resuscitation of a preterm neonate in the delivery room with 21% O2 and adjusting the O2 amount based on the transitional goal SpO2. As a natural extension of this work, now the candidate is focusing on what the optimal transitional goal SpO2 should be in preterm infants. Preliminary data from his previous work show that the current recommended transitional goal SpO2 (Ox50) may be too high and results in excess O2 exposure and oxidative stress in preterm neonates. The candidate hypothesizes that a low target O2 saturation strategy (Ox10-25) will result in successful resuscitation of preterm neonates with less O2 exposure and reduction in oxidative stress compared to the currently recommended high target O2 saturation strategy (Ox50). To test this hypothesis, a prospective, randomized, controlled trial of Ox10-25 versus Ox50 in 24-28 weeks gestational age infants will be conducted. The following three specific aims are proposed. To determine if Ox10-25 neonates will have decreased DR O2 exposure and early oxidative stress (Aim 1), will require less DR ventilatory support (Aim 2) and in turn will have reduced incidence of adverse clinical outcomes (Aim 3). This will be the first clinical trial evaluating two different transitioal SpO2 targets for preterm resuscitation in the DR. Preliminary data from this study will be used to design a larger clinical trial powered for neurodevelopmental outcomes which will form the basis of the candidate's R01 application toward the end of the K23 award. This study will provide critical information to optimize O2 therapy in the DR and has potential to improve clinical outcomes in preterm neonates.